Michael Croft's research works | University of Maine and other places

Lanthanide-induced toxicity in C. elegans. L1-stage N2 worms were treated with increasing concentrations of (top-left) LaCl3, (top-right) CeCl2, (bottom-left) ErCl3, or (bottom-right) YbCl3 for 30 min, washed, and transferred to agar plate supplemented with OP50 Escherichia coli. Survival was manually counted 48 h post-exposure and fit to a non-linear sigmoidal dose response. LD50 values were calculated and reported. Data points represent the mean + SEM from 5 independent experiments.

Lanthanides decrease DAergic function in C. elegans. L1-stage N2 worms were treated with lanthanides for 30 min, washed, and maintained on NGM agar plates seeded with OP50 E. coli. A total of 72 h post-exposure, worms were analyzed for the (A) BSR or (B) swim-to-crawl transition. (C) Alternatively, 30 h after reaching the L4 stage, eggs were quantified on agar or unlaid inside the worm. Data are presented as average (A) change in body bends on vs. off E. coli, (B) time to crawl, or (C) % eggs laid ± SEM of five independent experiments. * p < 0.05, ** p < 0.01, and *** p < 0.001 as compared to untreated control. Horizontal bars represent comparisons between concentrations of lanthanide-treated worms. # p < 0.05 and ### p < 0.001 as compared between lower and higher concentrations of lanthanides.

Lanthanides decrease serotonergic function in C. elegans. L1-stage (A) PE254 or (B) N2 worms were treated with lanthanides for 30 min, washed, and maintained on NGM agar plates seeded with OP50 E. coli. A total of 72 h post-exposure, worms were analyzed for (A) pharynx pump rate or (B) crawl-to-swim transition. Data are presented as average (A) rate of luminescence for 1 h and (B) time to swim ± SEM of five independent experiments. * p < 0.05, ** p < 0.01, and *** p < 0.001 as compared to untreated control. Horizontal bars represent comparisons between concentrations of lanthanide-treated worms. ## p < 0.01 as compared between lower and higher concentrations of lanthanides.

Lanthanides decrease dopamine and serotonin in C. elegans. (A) DA or (B) 5-HT was quantified immediately following exposure to La (III), Ce (III), Er (III), or Yb (III). Data are expressed as means ± SEM of five independent experiments. ** p < 0.01, and *** p < 0.001 as compared to untreated control. Horizontal bars represent comparisons between concentrations of lanthanide-treated worms. ## p < 0.01 and ### p < 0.001 as compared between lower and higher concentrations of lanthanides.

Lanthanides induce oxidative stress in C. elegans. Worms were treated for 30 min with La (III), Ce (III), Er (III), or Yb (III). Measures of oxidative stress were either assessed immediately (A) or 24 h following exposure (B–E). (A) ROS levels were assessed by DCFDA fluorescence. Data are expressed as mean fluorescence ± SEM for five independent experiments (B) AGE protein adducts were measured and normalized to protein content. Data are expressed as means ± SEM from 5 independent experiments. (C) Total GSH levels were quantified and normalized to protein content. Data are expressed as mean ± SEM from five independent experiments. (D) Quantification of GFP fluorescence of VP596 transgenic worms. Data are expressed as mean fluorescence ± SEM from 5 independent experiments. (E) ATP levels were quantified and normalized to protein content. Data are expressed as mean ± SEM from five independent experiments. * p < 0.05, ** p < 0.01, and *** p < 0.001 as compared with untreated control. Horizontal bars represent comparisons between concentrations of lanthanide-treated worms. # p < 0.05, ## p < 0.01, and ### p < 0.001 as compared between lower and higher concentrations of lanthanides.

Dopaminergic- and Serotonergic-Dependent Behaviors Are Altered by Lanthanide Series Metals in Caenorhabditis elegans

October 2024

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The lanthanide series elements are transition metals used as critical components of electronics, as well as rechargeable batteries, fertilizers, antimicrobials, contrast agents for medical imaging, and diesel fuel additives. With the surge in their utilization, lanthanide metals are being found more in our environment. However, little is known about the health effects associated with lanthanide exposure. Epidemiological studies as well as studies performed in rodents exposed to lanthanum (La) suggest neurological damage, learning and memory impairment, and disruption of neurotransmitter signaling, particularly in serotonin and dopamine pathways. Unfortunately, little is known about the neurological effects of heavier lanthanides. As dysfunctions of serotonergic and dopaminergic signaling are implicated in multiple neurological conditions, including Parkinson’s disease, depression, generalized anxiety disorder, and post-traumatic stress disorder, it is of utmost importance to determine the effects of La and other lanthanides on these neurotransmitter systems. We therefore hypothesized that early-life exposure of light [La (III) or cerium (Ce (III))] or heavy [erbium (Er (III)) or ytterbium (Yb (III))] lanthanides in Caenorhabditis elegans could cause dysregulation of serotonergic and dopaminergic signaling upon adulthood. Serotonergic signaling was assessed by measuring pharyngeal pump rate, crawl-to-swim transition, as well as egg-laying behaviors. Dopaminergic signaling was assessed by measuring locomotor rate and egg-laying and swim-to-crawl transition behaviors. Treatment with La (III), Ce (III), Er (III), or Yb (III) caused deficits in serotonergic or dopaminergic signaling in all assays, suggesting both the heavy and light lanthanides disrupt these neurotransmitter systems. Concomitant with dysregulation of neurotransmission, all four lanthanides increased reactive oxygen species (ROS) generation and decreased glutathione and ATP levels. This suggests increased oxidative stress, which is a known modifier of neurotransmission. Altogether, our data suggest that both heavy and light lanthanide series elements disrupt serotonergic and dopaminergic signaling and may affect the development or pharmacological management of related neurological conditions.

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Michael Croft’s research while affiliated with University of Maine and other places

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